Mammalian mitochondria contain 55S ribosomes of unusual composition and physical-chemical properties. The overall objective of the proposed research is to elucidate the unique functional properties of mammalian mitochondrial ribosomes. Most of the studies will be carried out using bovine mitochondrial ribosomes, as a model system for studies of mammalian mitochondrial ribosomes. Studies on the function of mitochondrial ribosomes will center on the mechanisms of initiation of protein synthesis. The specificity and requirements for finding of different mitochondrial mRNA molecules to mitoribosomal small subunits will be studied, and ribosomal proteins involved in mRNA binding will be identified through the use of affinity probes and studies on the functional reconstitution of protein-deficient particles. The extensive data base provided by these studies established the bovine mitochondrial ribosome as a comprehensive model system for studying ribosomes of mammalian mitochondria. These studies which elucidate the molecular components and functional groups that comprise active centers on mammalian mitochondrial ribosomes provide the basis for interpreting the toxic and adverse side effects of antibiotics and chemotherapeutic agents at the level of the mitochondrial ribosome.